ABCC8 p.Ser532Gly
| Predicted by SNAP2: | A: N (93%), C: N (93%), D: N (87%), E: N (93%), F: N (82%), G: N (93%), H: N (93%), I: N (93%), K: N (97%), L: N (93%), M: N (93%), N: N (97%), P: N (82%), Q: N (97%), R: N (87%), T: N (97%), V: N (97%), W: N (53%), Y: N (87%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: D, M: N, N: N, P: D, Q: N, R: N, T: N, V: D, W: D, Y: D, |
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[hide] Clinical characteristics and molecular genetic ana... Eur J Endocrinol. 2015 Jun;172(6):697-705. doi: 10.1530/EJE-14-0852. Epub 2015 Mar 9. Demirbilek H, Arya VB, Ozbek MN, Houghton JA, Baran RT, Akar M, Tekes S, Tuzun H, Mackay DJ, Flanagan SE, Hattersley AT, Ellard S, Hussain K
Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.
Eur J Endocrinol. 2015 Jun;172(6):697-705. doi: 10.1530/EJE-14-0852. Epub 2015 Mar 9., [PMID:25755231]
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BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.
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No. Sentence Comment
95 HM Permanent Yes No Normal NA No remission 15.18 KCNJ11 2 39/3000 4.8 Exon 1 c.602GOA (p.R201H) HT Permanent Yes No Normal Yes Successful transfer to SU therapy and weaned off insulin therapy 16.19 KCNJ11 13 40/2800 6.6 Exon 1 c.602GOA (p.R201H) HT Permanent No No Normal Yes Developmental delay, epilepsy, successful transfer to SU therapy and weaned off insulin therapy 17.20 ABCC8 3 40/2700 2.4 Exon 10 c.1594AOG (p.S532G) HT/novel Transient Yes No Normal NA Remission at the age of 3 months GW, gestation week; BW, birth weight; NDM, neonatal diabetes mellitus; HM, homozygous; HT, heterozygous; UPDPat6, paternal uniparental disomy on Chr6q24; F/H MD, family history of monogenic diabetes; EPI, exocrine pancreas insufficiency; SU-R, sulphonylurea response; SU, sulphonylurea. a Age at NDM diagnosis.
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ABCC8 p.Ser532Gly 25755231:95:419
status: NEW